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Titolo:
A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: Application to HLA in type 1 diabetes
Autore:
Cordell, HJ; Clayton, DG;
Indirizzi:
Univ Cambridge, Addenbrookes Hosp, Dept Med Genet,Cambridge Inst Med Res, JDRF WT Diabet & Inflammat Lab, Cambridge CB2 2XY, England Univ Cambridge Cambridge England CB2 2XY Lab, Cambridge CB2 2XY, England
Titolo Testata:
AMERICAN JOURNAL OF HUMAN GENETICS
fascicolo: 1, volume: 70, anno: 2002,
pagine: 124 - 141
SICI:
0002-9297(200201)70:1<124:AUSRPF>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
DISEASE-PREDISPOSING VARIANTS; TRANSMISSION/DISEQUILIBRIUM TEST; MAXIMUM-LIKELIHOOD; ASSOCIATION; REGION; RISK; MELLITUS; COMPLEX; MODELS; MHC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Cordell, HJ Univ Cambridge, Addenbrookes Hosp, Dept Med Genet,Cambridge Inst Med Res, JDRF WT Diabet & Inflammat Lab, Hills Rd, Cambridge CB2 2XY, England Univ Cambridge Hills Rd Cambridge England CB2 2XY XY, England
Citazione:
H.J. Cordell e D.G. Clayton, "A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: Application to HLA in type 1 diabetes", AM J HU GEN, 70(1), 2002, pp. 124-141

Abstract

A stepwise logistic-regression procedure is proposed for evaluation of therelative importance of variants at different sites within a small genetic region. By fitting statistical models with main effects, rather than modeling the full haplotype effects, we generate tests, with few degrees of freedom, that are likely to be powerful for detecting primary etiological determinants. The approach is applicable to either case/control or nuclear-familydata, with case/control data modeled via unconditional and family data viaconditional logistic regression. Four different conditioning strategies are proposed for evaluation of effects at multiple, closely linked loci when family data are used. The first strategy results in a likelihood that is equivalent to analysis of a matched case/control study with each affected offspring matched to three pseudocontrols, whereas the second strategy is equivalent to matching each affected offspring with between one and three pseudocontrols. Both of these strategies require parental phase (i.e., those haplotypes present in the parents) to be inferable. Families in which phase cannot be determined must be discarded, which can considerably reduce the effective size of a data set, particularly when large numbers of loci that arenot very polymorphic are being considered. Therefore, a third strategy is proposed in which knowledge of parental phase is not required, which allowsthose families with ambiguous phase to be included in the analysis. The fourth and final strategy is to use conditioning method 2 when parental phasecan be inferred and to use conditioning method 3 otherwise. The methods are illustrated using nuclear-family data to evaluate the contribution of loci in the HLA region to the development of type 1 diabetes.

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Documento generato il 09/12/19 alle ore 04:17:32